Page 627 - Advanced Organic Chemistry Part A - Structure and Mechanisms, 5th ed (2007) - Carey _ Sundberg

are considerably stronger bases, indicating better conjugation between the nitrogen 609
lone pair and the double bond. The reduced basicity of the cyclohexanone enamines
is related to the preference for exo and endo double bonds in six-membered rings. SECTION 6.5
Carbanions as
Nucleophiles in S N 2
(CH ) N H + (CH 2 ) n N + Reactions
2 n
n pK a
2 2.7
3 4.5
4 1.7

The preparation of enamines is discussed in Chapter 7, and their application as carbon
nucleophiles in synthesis is dealt with in Chapter 1 of Part B.

6.5. Carbanions as Nucleophiles in S 2 Reactions
N

Carbanions are very useful intermediates in the formation of carbon-carbon bonds.
This is true for both unstabilized structures found in organometallic reagents and
stabilized structures such as enolates. Carbanions can participate as nucleophiles in both
addition and substitution reactions. At this point we consider aspects of the reactions
of carbanions as nucleophiles in reactions that proceed by the S 2 mechanism. Other
N
synthetic applications of carbanions are discussed more completely in Chapter 7 and
in Chapters 1 and 2, Part B.

6.5.1. Substitution Reactions of Organometallic Reagents
Carbanions are classified as soft nucleophiles. They are expected to be good
nucleophiles in S 2 reactions and this is generally true. The reactions of aryl-, alkenyl- ,
N
and allyl lithium reagents with primary alkyl halides and tosylates appear to proceed by
S 2 mechanisms. Similar reactions occur between arylmagnesium halides (Grignard
N
reagents) and alkyl sulfates and sulfonates. Some examples of these reactions are given
in Scheme 6.2.
2
Note that all the examples in Scheme 6.2 involve either sp or stabilized
organometallic reagents. Evidence for an S 2-type mechanism in the reaction of allyl
N
and benzyl lithium reagents has been obtained from stereochemical studies. With
2-bromobutane, both of these reagents react with complete inversion of configu-
78
ration. n-Butyllithium, however, gives largely racemic product, indicating that some
competing process must also be occurring. 79 A general description of the mechanism
for the reaction of organolithium compounds with alkyl halides must take account
of the structure of the organometallic compound. It is known that halide anions are
accommodated into typical organolithium cluster structures and can replace solvent
molecules as ligands. A similar process in which the alkyl halide became complexed

78 L. H. Sommer and W. D. Korte, J. Org. Chem., 35, 22 (1970).
79
H. D. Zook and R. N. Goldey, J. Am. Chem. Soc., 75, 3975 (1953).